A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors
A partir d'une revue systématique de la littérature (50 articles identifiés), cette étude analyse la qualité des informations relatives aux événements indésirables de nature immunitaire dans les publications portant sur des essais cliniques d'évaluation d'inhibiteurs des points de contrôle immunitaire (CTLA-4 et autres)
Background There are limited data about the quality of immune related adverse event (irAE) reporting in immune checkpoint inhibitor (ICI) clinical trial publications. Methods A systematic search of citations from MEDLINE, EMBASE and Cochrane databases identified prospective clinical trials involving ICIs in advanced solid tumors from 2003-2013. A 21-point quality score (QS) was adapted from the CONSORT harms extension statement. Linear regression was used to identify factors associated with quality reporting. Results After a review of 2 628 articles, 50 trial reports were included, with ICIs as either monotherapy (54%) or part of a combination regimen (46%). The mean QS was 11.21 points (range 3.50 – 17.50 points). The median grade 3/4 AE rate reported was 21% (range 0-66%) and 29/50 (58%) trials concluded that irAEs were tolerable. Multivariate regression analysis revealed that year of publication (within last 5 years, P =.01) and journal impact factor >15 (P=.004) were associated with higher QS. Complete reporting of specific characteristics of irAEs including onset, management and reversibility were reported by 14%, 8%, and 6% of studies, respectively. The incidence of grade 3/4 adverse events was higher for inhibitors against CTLA-4 compared with other immune checkpoints (P<.001). Conclusion The reporting of irAEs is suboptimal. A standardized reporting method of irAEs that accounts for tolerability, management and reversibility is needed and would enable a more precise evaluation of the therapeutic risk benefit ratio of ICIs.
Annals of Oncology 2015